We have previously described a number of virulence factors produced by the bacterium Bordetella pertussis during the course of disease. These factors are regulated by the bvg locus and are coordinately expressed together with the more thoroughly studied virulence determinants filamentous hemagglutinin and pertussis toxin. Our studies have indicated that two of these proteins are virulence factors in the mouse aerosol challenge model of pertussis. We have cloned and sequenced the genes encoding these proteins. These proteins, which we have named Tcf and Bpf belong to a newly emerging family of proteins defined on the basis of a C-terminal tail that is highly conserved among members of this family. The function of the C-terminal tail of these proteins has not been determined, although it has been reported that the C-terminus of pertactin, the prototype of this family of proteins may be required for correct secretion across the bacterial cell envelope. Once secretion to the surface has occured a proteolytic cleavage event can occur to release the mature form of the protein from the 30 kDa C-terminus. The mature protein may remain loosely cell associated, as is pertactin, or released into the supernatant, as is Tcf. Bpf appears to utilize the C-terminal domain for secretion but does not contain a protease recognition site and thus the protein remains cell associated.A third bvg regulated protein has been identified as a porin-like protein. This protein appears to be a minor component of the bacterial cell envelope. Sequence analysis shows this protein, which we have named OmpQ to be more similar to the neisseria porin family than the enteric porin family.Our future studies will concentrate on the proteins Tcf and Bpf and their contribution to pathogenesis. We intend to determine the contribution of these proteins to protection using the mouse aerosol challenge model and to investigate the reponse of vaccinees to these proteins.
